Reelin is a glycoprotein that seems to have a role in central nervous system development. Reelin was discovered via studies of “reeler” mice, autosomal recessive mutants that have an ataxic and reeling gait. Reeler mice have numerous central nervous system defects, including cerebellar hypoplasia, abnormal neuronal positioning, aberrant orientation of cell bodies and fibers, inverted cortical lamination, and neuronal ectopia in laminated brain structures (e.g., cerebral and cerebellar cortices and hippocampus).
Neuroanatomical defects such as those observed in reeler mice can adversely affect synaptic connectivity and can impair normal brain function. Reelin levels are reportedly altered in the brains of some humans afflicted with major depression, bipolar disorder and schizophrenia, suggesting that Reelin may be involved in cell signaling systems underlying brain cognitive functions. See, e.g., Impagnatiello et al., 1998, Proc. Natl. Acad. Sci. USA, 95:15718-15723; Fatemi et al., 2000, Mol. Psychiatry, 5:654-663; Guidotti et al., Arch. Gen. Psychiatry, 57:1061-9; and Fatemi et al., 2001 Neuro. Report, 12:3209-3215.